Biosynthesis of the Siderophore Rhodochelin Requires the Coordinated Expression of Three Independent Gene Clusters in <i>Rhodococcus jostii</i> RHA1

Bosello, Mattia; Robbel, Lars; Linne, Uwe; Xie, Xiulan; Marahiel, Mohamed A.

doi:10.1021/ja1109453

Cited by 57 publications

(86 citation statements)

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“…The rhodococcal siderophores characterized to date (heterobactin A, rhodobactin, and rhodochelin) all contain ornithine or modified ornithine residues (4,7,14). The remaining genes in this gene cluster are predicted to encode proteins required for the modification of ornithine by formylation and hydroxylation (RhbA and RhbD), amino acid activation (RhbE), and release of the tetrapeptide from the NRPS (RhbB).…”

Section: Discussionmentioning

confidence: 99%

“…The synthesis of rhequibactin depends on a six-cistron operon containing two NRPS genes, iupS and iupT, and four genes encoding siderophore biosynthesis and transport proteins. Upstream and transcribed divergently of this operon is a four-cistron operon encoding enzymes required for the production of 2,3-dihydroxybenzoic acid, which is also present in the mixed-type catecholate-hydroxamate siderophores heterobactin A, rhodobactin, and rhodochelin produced by R. erythropolis, R. rhodochrous, and R. jostii, respectively (4,7,14). In addition to rhequibactin, R. equi appears to synthesize a nonsoluble siderophore that is produced by an NRPS protein encoded by iupU (30).…”

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confidence: 99%

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The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

et al. 2012

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We previously showed that the facultative intracellular pathogen Rhodococcus equi produces a nondiffusible and catecholatecontaining siderophore (rhequibactin) involved in iron acquisition during saprophytic growth. Here, we provide evidence that the rhbABCDE cluster directs the biosynthesis of a hydroxamate siderophore, rhequichelin, that plays a key role in virulence. The rhbC gene encodes a nonribosomal peptide synthetase that is predicted to produce a tetrapeptide consisting of N 5 -formyl-N 5 -hydroxyornithine, serine, N 5 -hydroxyornithine, and N 5 -acyl-N 5 -hydroxyornithine. The other rhb genes encode putative tailoring enzymes mediating modification of ornithine residues incorporated into the hydroxamate product of RhbC. Transcription of rhbC was upregulated during growth in iron-depleted medium, suggesting that it plays a role in iron acquisition. This was confirmed by deletion of rhbCD, rendering the resulting strain R. equi SID2 unable to grow in the presence of the iron chelator 2,2-dipyridyl. Supernatant of the wild-type strain rescued the phenotype of R. equi SID2. The importance of rhequichelin in virulence was highlighted by the rapid increase in transcription levels of rhbC following infection and the inability of R. equi SID2 to grow within macrophages. Unlike the wild-type strain, R. equi SID2 was unable to replicate in vivo and was rapidly cleared from the lungs of infected mice. Rhequichelin is thus a key virulence-associated factor, although nonpathogenic Rhodococcus species also appear to produce rhequichelin or a structurally closely related compound. Rhequichelin biosynthesis may therefore be considered an example of cooption of a core actinobacterial trait in the evolution of R. equi virulence.

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Section: Discussionmentioning

confidence: 99%

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The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

et al. 2012

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“…The production of the serratiochelins by Serratia plymuthica V4, for example, relies on two BGCs, only one of which encodes for the catechol[31]. And, the siderophore rhodochelin from Rhodococcus jostii RHA1 uses three BGCs to generate a non-ribosomal peptide scaffold that includes a 2,3-dihydroxybenzoic acid and two hydroxamates[32]. The range of molecules whose biosynthesis requires more than one pathway is unknown, but it is likely that the reports on this genetic strategy are underrepresented in the literature.…”

Section: Lessons From Chemical Ecologymentioning

confidence: 99%

Gene Flow and Molecular Innovation in Bacteria

Ruzzini

Clardy

2016

Current Biology

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Summary The small molecules produced by environmental bacteria have been mainstays of both chemical and biological research for decades, and some have lead to important therapeutic interventions. These small molecules have been shaped by natural selection as they evolved to fulfill changing functional roles in their native environments. This minireview describes some recent systematic studies providing illustrative examples that involve the acquisition and alteration of genetic information for molecular innovation by bacteria in well-defined environments. Two different bacterial genera are featured, Pseudonocardia and Salinispora, and while the small molecule repertoires of both have benefited from horizontal gene transfer, Pseudonocardia spp. have relied on plasmid-based tactics while Salinispora spp. have relied on chromosomally integrated genomic islands.

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“…The biosynthesis of different secondary metabolites by a microorganism is often coordinated (Bosello et al, 2011; Tsunematsu et al, 2013; Hidalgo et al, 2014; Vingadassalon et al, 2015; Cano-Prieto et al, 2015; Cui et al, 2016). Co-regulation of different secondary metabolites is thought to be selected during microbial evolution because it confers competitive advantages to the producing organism in microbial interactions (Challis and Hopwood, 2003).…”

Section: Introductionmentioning

confidence: 99%

Novel mechanism of metabolic co-regulation coordinates the biosynthesis of secondary metabolites in Pseudomonas protegens

Yan

Philmus

Chang

et al. 2017

eLife

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Metabolic co-regulation between biosynthetic pathways for secondary metabolites is common in microbes and can play an important role in microbial interactions. Here, we describe a novel mechanism of metabolic co-regulation in which an intermediate in one pathway is converted into signals that activate a second pathway. Our study focused on the co-regulation of 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin, two antimicrobial metabolites produced by the soil bacterium Pseudomonas protegens. We show that an intermediate in DAPG biosynthesis, phloroglucinol, is transformed by a halogenase encoded in the pyoluteorin gene cluster into mono- and di-chlorinated phloroglucinols. The chlorinated phloroglucinols function as intra- and inter-cellular signals that induce the expression of pyoluteorin biosynthetic genes, pyoluteorin production, and pyoluteorin-mediated inhibition of the plant-pathogenic bacterium Erwinia amylovora. This metabolic co-regulation provides a strategy for P. protegens to optimize the deployment of secondary metabolites with distinct roles in cooperative and competitive microbial interactions.DOI: http://dx.doi.org/10.7554/eLife.22835.001

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Biosynthesis of the Siderophore Rhodochelin Requires the Coordinated Expression of Three Independent Gene Clusters in Rhodococcus jostii RHA1

Cited by 57 publications

References 46 publications

The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

Gene Flow and Molecular Innovation in Bacteria

Novel mechanism of metabolic co-regulation coordinates the biosynthesis of secondary metabolites in Pseudomonas protegens

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